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Early Phase 1 N=35 Randomized Double-blind Basic Science

Remediation of Impaired Self-Regulation in Patients With Mild TBI

Mild Traumatic Brain Injury

Enrolled (actual)
35
Serious AEs
0.0%
Results posted
Sep 2025
Primary outcome: Primary: Blood Oxygen Level Dependent (BOLD) Brain Signal Measured Using Functional MRI. — 270; 111 voxels — p=<0.0001

Study Design & Population

Study type
Interventional
Phase
Early Phase 1
Interventions
Tolcapone (Drug); Placebo (Drug)
Age
Adult · 18+ yrs
Sex
All
Sponsor
VA Office of Research and Development
Primary completion
Jun 2021

Outcome Measures

OutcomeResultp-value
PRIMARY
Blood Oxygen Level Dependent (BOLD) Brain Signal Measured Using Functional MRI.
270; 111 <0.0001 sig
PRIMARY
Performance on Cognitive Testing
25.4; 25.4 0.0184 sig

Summary

The ability to regulate impulses enables us to plan for the future, to maintain focus in the face of distractions (i.e. to encode memories), and to manage emotions. This self regulation can be compromised in individuals who have a history of mild traumatic brain injury and co-occurring disorders. In this study the investigators are using functional MRI scanning to understand how memory and self regulation are expressed in the brains of people with a history of mild traumatic brain injury. The investigators are also testing whether the medication tolcapone may improve memory and self regulation.

Eligibility Criteria

Inclusion Criteria

  • Veteran ages 18-50 and in general good health;
  • Able to read English at a 6th grade level;
  • Able to provide written informed consent;
  • Normal or corrected to normal visual acuity;
  • Stable doses of all medications (2 weeks or greater);
  • History of mild traumatic brain injury greater than 6 months prior to participation

Exclusion Criteria

  • Contraindications to magnetic resonance imaging (MRI) scanning;
  • Inability to complete basic fMRI requirements;
  • History of brain surgery or penetrating brain injury;
  • Uncontrolled blood pressure (low or high);
  • Contraindications to tolcapone use;
  • Use of medications or drugs with dopamine-related actions within 30 days;
  • Active substance abuse or dependence;
  • Clinically severe medical illness requiring treatment;
  • History of psychiatric hospitalization (past 1 year) or suicide attempt (past 5 years);
  • Seizures greater than 4 weeks after traumatic brain injury (TBI) event or seizures requiring active treatment;
  • History of brain tumor, stroke, Alzheimer's disease, aneurysm rupture, or multiple sclerosis;
  • History of schizophrenia, attention deficit hyperactivity disorder (ADHD) or psychiatric diagnosis EXCEPT depression or post-traumatic stress disorder (PTSD)
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02260570). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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